Psoriatic arthritis, axial spondyloarthritis and rheumatoid arthritis in Norway: nationwide prevalence and use of biologic agents.

OBJECTIVE: To estimate the prevalence of psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA) and the use of biologic agents in these diseases in Norway. METHODS: From the Norwegian Patient Registry (NPR), we identified as PsA, axSpA and RA patients ≥18 years those with ≥2 recorded episodes with diagnostic coding for index disease (L40.5, M07.0-M07.3 for PsA; M45, M46.0, M46.1, M46.8 and M46.9 for axSpA; M05-M06 for RA). We calculated the point prevalence of PsA, axSpA and RA as per the 1st of January 2017 in the Norwegian adult population (age ≥18). Dispensed disease-modifying antirheumatic drug (DMARD) prescriptions were obtained from the Norwegian Prescription Database and biologic DMARDs given in hospitals from the NPR. RESULTS: The point prevalence of PsA, axSpA, RA, and any of these diseases in total was 0.46%, 0.41%, 0.78%, and 1.56%, respectively. Among women, the prevalence of PsA, axSpA, and RA was 0.50%, 0.37%, and 1.10%, and among men 0.43%, 0.45%, and 0.46%, respectively. In 2017, 27.3% of RA patients, 25.7% of PsA patients and 35.1% of axSpA patients used biologic DMARDs. Treatment with biologics was more frequent in younger age groups in all three diseases, and became more infrequent especially after age ≥55 years. CONCLUSION: In Norway, the combined prevalence of PsA, axSpA, and RA was over 1.5%. Reflecting the good overall access to highly effective but costly biologic treatments, more than a fourth of these patients used biologic agents, which corresponds to over 0.4% of Norwegian adult population.

Serum golimumab concentration and anti-drug antibodies are associated with treatment response and drug survival in patients with inflammatory joint diseases: data from the NOR-DMARD study.

Objectives: This study aimed to identify the therapeutic target concentration and frequency of anti-drug antibodies (ADAbs) in golimumab-treated patients with inflammatory joint disease (IJD).Method: Associations between golimumab concentration, ADAbs, and treatment response were examined in 91 patients with IJD [41 axial spondyloarthritis (axSpA), 20 rheumatoid arthritis (RA), and 30 psoriatic arthritis (PsA)] included in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement in axSpA, European League Against Rheumatism (EULAR) good/moderate response in RA, and improvement of ≥ 50% in modified Disease Activity index for PSoriatic Arthritis (DAPSA) (28 swollen/tender joint counts) in PsA. Serum drug concentrations and ADAbs were analysed using automated in-house assays.Results: At inclusion, 42% were biological disease-modifying anti-rheumatic drug naïve and 42% used concomitant synthetic disease-modifying anti-rheumatic drug. The median golimumab concentration was 2.2 (interquartile range 1.0-3.5) mg/L. The proportions of responders after 3 months among patients with golimumab concentration < 1.0, 1.0-3.9, and ≥ 4.0 mg/L were 19%, 49%, and 74%, respectively. A higher rate of treatment discontinuation was seen in patients with serum golimumab concentration < 1.0 compared to ≥ 1.0 mg/L (hazard ratio 3.3, 95% confidence interval 1.8-6.0, p < 0.05). ADAbs were detected in 6%, and were associated with lower drug concentrations and both reduced treatment response and drug survival.Conclusions: Golimumab concentrations ≥ 1.0 mg/L were associated with improved treatment response and better drug survival, although some patients may benefit from higher concentrations. This study suggests a rationale for dosing guided by therapeutic drug monitoring in golimumab-treated patients with IJD. The results should be confirmed in larger studies including trough samples, and the efficacy of such a strategy must be examined in randomized controlled trials.

Smoking and response to rituximab in rheumatoid arthritis: results from an international European collaboration.

OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.

Secukinumab provides sustained PASDAS-defined remission in psoriatic arthritis and improves health-related quality of life in patients achieving remission: 2-year results from the phase III FUTURE 2 study.

BACKGROUND: Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study. METHODS: PASDAS (cut-off scores: remission ≤ 1.9; LDA > 1.9 and < 3.2; Moderate Disease Activity ≥ 3.2 and < 5.4; and high disease activity [HDA] ≥ 5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150 mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. RESULTS: In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300 mg and in 15.2% and 19.2%, respectively, in the secukinumab 150 mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission + LDA at week 16 with secukinumab 300 and 150 mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2 years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2 years. CONCLUSIONS: Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2 years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.

Smoking and alcohol use are associated with structural and inflammatory hand osteoarthritis features.

OBJECTIVES: To explore whether smoking and alcohol use are associated with hand osteoarthritis (OA) features in two different OA cohorts. METHOD: We studied 530 people with radiographic hand OA from the Musculoskeletal pain in Ullensaker STudy (MUST) and 187 people from the Oslo hand OA cohort [mean (sd) age 65 (8.0) and 62 (5.7) years, 71% and 91% women, respectively]. Smoking, alcohol use and hand pain were self-reported. Participants underwent conventional hand radiographs and ultrasound examination of 30 hand joints. The Kellgren-Lawrence sum score for radiographic OA severity (0-120 scale) and the proportion of participants having at least one joint with grey-scale synovitis (grade ≥1) were calculated. We studied whether smoking and alcohol use were cross-sectionally associated with radiographic OA, synovitis, and pain using adjusted linear and logistic regression analyses. RESULTS: Smoking was associated with less radiographic OA in both cohorts [ß = -4.71, 95% confidence interval (CI) -8.36 to -1.06 for current smoking in MUST and ß = -0.15, 95% CI -0.29 to -0.02 for smoking pack-years in the Oslo hand OA cohort]. Stratified analyses indicated that the association was present in men only. Being a monthly drinker (examined in MUST only) was significantly associated with present synovitis compared to never drinkers (odds ratio = 2.35, 95% CI 1.27 to 4.34) (no gender differences). Neither smoking nor alcohol was associated with hand pain. CONCLUSIONS: Smoking was associated with less radiographic hand OA whereas alcohol consumption was associated with present joint inflammation in hand OA. Future longitudinal studies are needed to explore the causal associations and explanatory mechanisms behind gender differences.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Circulating levels of inflammatory cytokines and cytokine receptors in patients with ankylosing spondylitis: a cross-sectional comparative study.

OBJECTIVES: Insight into the most important inflammatory pathways in ankylosing spondylitis (AS) could be of importance in risk stratification and the development of treatment strategies. Therefore, we aimed to compare circulating levels of inflammatory biomarkers between AS patients and controls, and explore associations between these biomarkers and clinical measures of disease activity. METHOD: In a cross-sectional study, 143 AS patients were compared with 124 population controls. Blood samples were analysed by immunoassays for interleukin (IL)-6, IL-17a, IL-23, soluble tumour necrosis factor receptor 1 (sTNF-R1) and 2 (sTNF-R2), and osteoprotegerin (OPG). Disease activity was measured by the AS Disease Activity Score (ASDAS) and the Bath AS Disease Activity Index (BASDAI). RESULTS: Analysis of covariance (ANCOVA) demonstrated elevated plasma levels of sTNF-R1 [geometrical mean 0.94 (95% CI 0.88-1.00) vs. 0.83 (95% CI 0.78-0.89) ng/mL, p < 0.01] and OPG (2.3, 95% CI 2.1-2.4 vs. 2.0, 95% CI 1.9-2.2 ng/mL, p = 0.02) and, although not significant, of IL-23 (122, 95% CI 108-139 vs. 106, 95% CI 93-120 pg/mL, p = 0.07) in AS patients vs. CONTROLS: More AS patients had a high level of sTNF-R2 than controls (22 vs. 1, p < 0.01). No differences between the groups were seen for IL-6 and IL-17a. In patients, no significant associations were seen between inflammatory markers and disease activity measures after adjusting for personal characteristics. CONCLUSION: Significantly higher plasma levels of sTNF-R1, sTNF-R2, and OPG and numerically but non-significantly higher levels of IL-23 were found in AS patients compared to controls, indicating that these cytokines and cytokine receptors are important inflammatory pathways. Clinical measures of disease activity were not significantly correlated with circulating inflammatory markers.

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.

BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.

Cost-effectiveness analyses of elective orthopaedic surgical procedures in patients with inflammatory arthropathies.

OBJECTIVE: To examine the costs per quality-adjusted life year (QALY) gained for surgical interventions in patients with inflammatory arthropathies, and to compare the costs per QALY gained for replacement versus non-replacement surgical interventions. METHODS: In total, 248 patients [mean age 57 (SD 13) years, 77% female] with inflammatory arthropathies underwent orthopaedic surgical treatment and responded to mail surveys at baseline and during follow-up (3, 6, 9, and 12 months). Questionnaires included the quality-of-life EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) utility scores. The health benefit from surgery was subsequently translated into QALYs. The direct treatment costs in the first year were, for each patient, derived from the hospital's cost per patient accounting system (KOSPA). The costs per QALY were estimated and future costs and benefits were discounted at 4%. RESULTS: Improvement in utility at 1-year follow-up was 0.10 with EQ-5D and 0.03 with SF-6D (p < 0.05). The estimated 10-year cost per QALY gained was EUR 5000 for hip replacement surgery (EUR18 600 using SF-6D) and EUR 10 500 (EUR 48 500 using SF-6D) for all replacement procedures. The 5-year cost per QALY was EUR 17 800 for non-replacement surgical procedures measured by EQ-5D (SF-6D: EUR 67 500). CONCLUSIONS: Elective orthopaedic surgery in patients with inflammatory arthropathies was cost-effective when measured with EQ-5D, and some procedures were also cost-effective when SF-6D was used in the economic evaluations. Hip replacement surgery was most cost-effective, irrespective of the method of analysis.

Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register.

OBJECTIVE: To assess the effectiveness of switching to a second tumour necrosis factor inhibitor (TNFi) in patients with ankylosing spondylitis (AS). METHODS: Data were extracted from an ongoing longitudinal observational multicentre study in Norway. This study included anti-TNF naïve patients with AS starting treatment with a TNFi as well as treatment with a second TNFi in these same patients. Effectiveness data and 2-year drug survival were compared between switchers and non-switchers and within switchers (first and second TNFi). RESULTS: 514 anti-TNF naïve patients with AS were included; 77 patients switched to a second TNFi while 437 patients did not switch. The percentages of non-switchers using etanercept, infliximab or adalimumab were 53%, 32% and 15%, and the percentages of first and second TNFi in the switchers were 42%, 53% and 5% and 40%, 23% and 36%, respectively. The reason for switching was insufficient response (IR) in 30, adverse events (AEs) in 44 and not reported in 3 patients. Baseline disease activity was similar between the groups. Three-month BASDAI 50 and ASAS 40 responses were achieved by 49% and 38% of non-switchers, by 25% and 30% of switchers after the first TNFi and by 28% and 31% after the second TNFi. The 3-month disease activity level was higher for switchers on the second TNFi than for non-switchers. Drug withdrawal rate was higher during the second TNFi among switchers than for non-switchers (p=0.001). No difference was found in the effectiveness of the second TNFi between switchers due to IR and AE. CONCLUSION: This study confirms that switching to a second TNFi can be effective in AS and can be as useful as in rheumatoid arthritis, although overall effectiveness seems to be somewhat lower than in non-switchers.

Ultrasonography shows significant improvement in wrist and ankle tenosynovitis in rheumatoid arthritis patients treated with adalimumab.

OBJECTIVE: Tenosynovitis is common in rheumatoid arthritis (RA) but knowledge is limited regarding its response to anti-inflammatory treatment. This study used ultrasonography (US) to examine the distribution and responsiveness of tenosynovitis to anti-tumour necrosis factor (anti-TNF) treatment in RA patients. METHODS: Twenty patients with RA were examined at baseline and 1, 3, 6, and 12 months after starting adalimumab treatment, and grey-scale (GS) and power Doppler (PD) US scoring (semi-quantitative range 0-3) of wrist and ankle tendons was performed in addition to assessment of the 28-joint Disease Activity Score (DAS28), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: The extensor carpi ulnaris (ECU) tendon in the wrists and the closely related tendons tibialis posterior (TB) and flexor digitorum longus (FDL) in the ankles were most often inflamed. Median sum scores for this reduced number of tendons at baseline/12-month follow-up were 5/0.5 for GS (p < 0.001) and 4/0 for PD (p < 0.05), with reductions in the US scores during follow-up as large as those found for sum scores of all tendons. The standardized response means (SRMs) for sum GS or PD scores of the reduced number of tendons were higher (range -0.53 to -0.93) than for the sum scores of all tendons (-0.23 to -0.74), and showed larger responsiveness than CRP (-0.10 to -0.43) and ESR (-0.03 to -0.71). CONCLUSION: Bilateral assessments of ECU, TB, and FDL tendons were as sensitive to change as the sum scores of all tendons, and scoring of this reduced number of tendons is suggested to be included in US scorings for follow-up of RA patients.

Patients with inflammatory arthropathies undergo feet surgery later in the disease course than hand surgery.

OBJECTIVES: Inflammatory arthropathies often results in functional impairment and joint damage and deformity. Hand and foot are frequent locations for surgical interventions. Our objective is to compare disease duration, patient reported health status measures and use of medication in patients with inflammatory arthropathies referred for hand or foot surgery. METHODS: Patients referred for hand or foot surgery at the Diakonhjemmet Hospital responded to mail surveys preoperatively, including AIMS2, HAQ, SF-36, EQ-5, and visual analogue scales addressing patient global assessment of disease activity, fatigue, general pain and pain in the actual joint. Data on disease duration, surgical treatment and medication were collected from the hospital records. RESULTS: 116 patients (mean (SD) age 57 (13) years, 76% female) with inflammatory arthropathies underwent hand (n=52, mean (SD) age 55 (13) years) or foot (n=64, mean (SD) age 58 (13) years) surgery. Disease duration at the time of surgery was significantly longer for patients referred for foot vs. hand surgery (19 (13) vs. 13 (10) years, p=0.04). Patients undergoing foot surgery used more frequently biological or conventional disease-modifying antirheumatic drug at the time of surgery than patients having hand surgery (50% vs. 71%, respectively, p=0.02). Baseline values for the patient-reported health status measures were mainly similar for the two patient groups. CONCLUSIONS: Patients undergoing surgical procedures in the foot had significantly longer disease duration and were more frequently on potent medication at the time of surgery than patients undergoing hand surgery. The observation may indicate that the impact of foot damage in inflammatory arthropathies is underestimated.

EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis.

OBJECTIVES: To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. RESULTS: Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. CONCLUSIONS: Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.

Health status and perception of pain: a comparative study between female patients with hand osteoarthritis and rheumatoid arthritis.

OBJECTIVE: Osteoarthritis (OA) is the most frequent rheumatic joint disease and its occurrence is growing due to prolonged life expectancy and an increasing number of elderly individuals in the population. The main objective of this study was to compare the burden of disease, assessed by measures of pain and health-related quality of life (HRQoL), between female patients with hand osteoarthritis (HOA) and rheumatoid arthritis (RA). METHODS: One hundred and ninety female HOA patients were compared with 194 female RA patients of the same age. HRQoL was measured with the Arthritis Impact Measurement 2 Scale (Aims2), the 36-item Short-Form Health Survey (SF-36) and its preference-based single index measure SF-6D, the Health Assessment Questionnaire (HAQ), the modified HAQ (MHAQ), self-efficacy scales, and visual analogue scales (VAS) for pain and fatigue. We also compared levels of fibromyalgia (FM)-like symptoms (headache, muscle pain, numbness, and concentration problems). Scores were compared by a multivariate analysis of covariance (ANCOVA), adjusted for age, number of comorbidities, and years of education. Sime's procedure was used to adjust for multiple testing. RESULTS: RA patients had significantly lower levels of physical functioning compared to HOA patients, whereas pain measured on the Arthritis Impact Measurement Scale 2 (AIMS2) was significantly worse in HOA as compared with RA. The HOA patients also had worse scores for FM-like symptoms. SF-6D utility scores in HOA and RA were similar (0.63 and 0.64, respectively). CONCLUSIONS: The overall impact of the disease on HRQoL was similar between RA and HOA patients, based on the SF-6D scores. Physical function was worse in RA patients, but HOA patients reported worse scores in pain measures and FM-like symptoms.

Comparison of work disability and health-related quality of life between males and females with rheumatoid arthritis below the age of 45 years.

OBJECTIVES: To compare work disability (WD) and health status between males and females with rheumatoid arthritis (RA) in the age group 18-45 years, and to compare health status between patients with and without WD within each gender, and finally to identify factors independently associated with WD in this age group. METHODS: A cross-sectional study of RA patients at the time starting with disease-modifying antirheumatic drug (DMARD) therapy and/or biological treatment. Patients receiving a permanent, national WD pension corresponding to >or= 50% were defined as work disabled. We examined gender differences with regard to disease characteristics, health status and WD. The Mann-Whitney U-test and Pearson's chi(2)-test were applied for group comparisons. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score [using the Modified Health Assessment Questionnaire (MHAQ)], Disease Activity Score-28 (DAS-28), the Short Form Health Survey (SF-36) mental health score and gender were used to identify variables associated with WD. RESULTS: Out of 474 (372 females) patients, the number (%) of work-disabled females/males was 91 (24.7)/8 (8.1) (p<0.001). WD was associated with worse health status in both genders. The odds ratio (95% confidence interval) [OR (95% CI)] for WD in females vs. males was 4.84 (1.85-12.65) in the multivariate analyses. Other factors independently associated with WD were worse mental health, disease duration and low level of education. CONCLUSION: Females with RA had a fourfold increased risk of WD compared to men. Low level of education, disease duration and worse mental health were also independently associated with WD.

Orthopaedic surgery in 255 patients with inflammatory arthropathies: longitudinal effects on pain, physical function and health-related quality of life.

OBJECTIVE: To examine the effectiveness of orthopaedic surgery in patients with inflammatory arthropathies with regard to longitudinal changes in pain, physical function and health-related quality of life and explore differences in effectiveness between replacement versus non-replacement surgery and surgery in the upper versus the lower limb. METHODS: 255 patients (mean age 57.5 years (SD 13.1), 76.7% female) with inflammatory arthropathies underwent orthopaedic surgical treatment and responded to mail surveys at baseline and during follow-up (3, 6, 9 and 12 months). The booklet of questionnaires included the arthritis impact measurement scales 2 (AIMS2), health assessment questionnaire (HAQ), short form 36 (SF-36), EQ-5D and visual analogue scales (VAS) addressing patient global, fatigue, general pain and pain in the actual joint. Standardised response means (SRM) were calculated to estimate the magnitude of improvement. RESULTS: Significant improvement was seen for most of the dimensions of health, the largest improvement for pain in the actual joint (SRM 1.17) at one year follow-up. SRM for AIMS-2 physical, SF-36 physical and HAQ were 0.1, 0.48 and 0.05, respectively. The overall numeric improvement (SRM) in utility was 0.10 (0.37) with EQ-5D and 0.03 (0.27) with SF-6D. Improvement overall was similar after surgery in the upper versus the lower limb, but was larger in patients undergoing replacement surgery than in patients undergoing other surgical procedures (SRM 1.54 vs 1.08 for pain in the actual joint). CONCLUSIONS: Surgical procedures have a major positive impact on pain in the actual joint, but improvement is less in other dimensions of health. Health benefits were larger after replacement surgery than after other surgical procedures.

ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis.

OBJECTIVES: To evaluate various validity aspects of four disease activity scores (ASDAS) for ankylosing spondylitis (AS) in comparison with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), its individual components and physician and patient global assessment of disease activity. METHODS: The analyses were performed in two cohorts of patients with AS: (1) the NOR-DMARD database which includes patients starting on a disease-modifying antirheumatic drug or tumour necrosis factor (TNF) blocker and (2) patients participating in double-blind placebo controlled randomised clinical trials with TNF blockers in four centres. Discrimination between patients with low versus high disease activity according to various definitions and between various levels of change were analysed as the standardised mean difference (difference in the group means divided by the pooled SD of the group means) and t score. RESULTS: The four ASDAS versions were highly discriminatory in differentiating patients with different levels of disease activity and patients with different levels of change. The ASDAS scores outperformed the BASDAI and its single components in all settings: patient- or physician-based, reflecting status or change, with normal or raised C-reactive protein (CRP), in the presence or absence of peripheral arthritis. There were no major differences between the four ASDAS scores. Based on feasibility, the ASAS membership selected the ASDAS version which included back pain, duration of morning stiffness, patient global assessment, peripheral joint complaints and CRP as the preferred version. CONCLUSIONS: The ASDAS is a validated, highly discriminatory instrument for assessing disease activity in AS, including patient-reported outcomes and CRP levels.

Monitoring anti-TNFalpha treatment in rheumatoid arthritis: responsiveness of magnetic resonance imaging and ultrasonography of the dominant wrist joint compared with conventional measures of disease activity and structural damage.

OBJECTIVES: To evaluate the responsiveness of magnetic resonance imaging (MRI) and ultrasonography (US) compared with conventional measures of disease activity and structural damage in patients with rheumatoid arthritis (RA) during the first year of treatment with anti-tumour necrosis factor alpha (TNFalpha). METHODS: A cohort of patients with RA (N = 36, median age 53 years, disease duration 7.6 years and disease activity score (DAS28) 5.7) was evaluated by core measures of disease activity, US (one wrist), MRI (one wrist) and conventional radiography (CR, both hands and wrists) at initiation of treatment with anti-TNFalpha agents and after 3, 6 and 12 months. Responsiveness was assessed by standardised response means (SRM). Accepted thresholds were applied to classify responsiveness as trivial, low, moderate or good. RESULTS: MRI synovitis (SRM between -0.79 and -0.92) and the MRI total inflammation score comprising synovitis, tenosynovitis and bone marrow oedema (SRM between -1.05 and -1.24) were highly responsive. Moderate to high responsiveness was found for MRI tenosynovitis and bone marrow oedema, all the composite indices (DAS28, simplified disease activity index (SDAI) and clinical disease activity index (CDAI)) and the 28-swollen joint count. US displayed low to moderate responsiveness. The MRI erosion score displayed low responsiveness but was more responsive than CR measures at 3 and 6 months follow-up. MRI and CR measures of annual progression rates of damage performed similarly and were highly responsive. CONCLUSIONS: The most responsive measure of inflammation when evaluating anti-TNFalpha medication was a composite measure comprising MRI synovitis, tenosynovitis and bone marrow oedema, and this may be a promising outcome measure in clinical studies.

Impact of adalimumab on work participation in rheumatoid arthritis: comparison of an open-label extension study and a registry-based control group.

BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) causes considerable disability and often results in loss of work capacity and productivity. This study evaluated the impact of adalimumab, a tumour necrosis factor antagonist with demonstrated efficacy in RA, on long-term employment. METHODS: Data from an open-label extension study (DE033) of 486 RA patients receiving adalimumab monotherapy who previously did not respond to at least one disease-modifying antirheumatic drug (DMARD) and had baseline work status information were compared with data from 747 RA patients receiving DMARD treatment in a Norway-based longitudinal registry. Primary outcomes included the time patients continued working at least part time and the likelihood of stopping work. Secondary outcomes included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) responses and disease remission. Outcomes were compared 6, 12 and 24 months after enrolment. RESULTS: During a 24-month period, the 158 patients who received adalimumab and were working at baseline worked 7.32 months longer (95% CI 4.8 to 9.1) than did the 180 patients treated with DMARDs, controlling for differences in baseline characteristics. Regardless of baseline work status, patients receiving adalimumab worked 2.0 months longer (95% CI 1.3 to 2.6) and were significantly less likely to stop working than those receiving DMARDs (HR 0.36 (95% CI -0.30 to 0.42) for all patients and 0.36 (95% CI 0.15 to 0.85) for patients working at baseline, respectively). The patients who received adalimumab were also considerably more likely to achieve ACR responses and disease remission than DMARD-treated patients. Patients who achieved EULAR good response and remission were less likely to stop working, but this relationship was only seen in patients receiving DMARDs. CONCLUSIONS: Patients with RA who received adalimumab experienced considerably longer periods of work and continuous employment, and greater rates of clinical responses, than patients receiving DMARDs. The mechanism by which adalimumab decreases likelihood of stopping work seems to be different from that of DMARD treatment and independent of clinical responses.

Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies.

OBJECTIVE: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56. RESULTS: Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001). CONCLUSIONS: This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.